Semax, an analogue of adrenocorticotropin (4-10), is a potential agent for the treatment of attention-deficit hyperactivity disorder and Rett syndrome

Med Hypotheses. 2007;68(5):1144-6. doi: 10.1016/j.mehy.2006.07.017. Epub 2006 Sep 25.


Psychostimulants, such as methylphenidate, are currently the most common used drug therapy for children with attention-deficit hyperactivity disorder (ADHD). However, a number of patients with ADHD either fail to respond to these drugs or experience side effects that preclude their use. The heptapeptide Semax is an analogue of the N-terminal fragment (4-10) of adrenocorticotropic hormone, but is completely devoid of any hormonal activity. It has been found to stimulate memory and attention in rodents and humans after intranasal application. Evidence from animal studies revealed that Semax can augment the effects of psychostimulants on central dopamine release and also stimulates central brain-derived neurotrophic factor (BDNF) synthesis. In addition, Semax could improve selective attention and modulate brain development. Since ADHD is likely to be a neurodevelopmental disorder with disturbance in dopamine and BDNF function, it is proposed in this paper that Semax may have good therapeutic potential in ADHD. Furthermore, increased BDNF activity is found to improve Rett syndrome, a severe neurodevelopmental disorder which is, in the majority of cases, caused by mutations in the gene encoding methyl-CpG-binding protein 2 (MECP2). The potential therapeutic effect of Semax in Rett syndrome by increasing central BDNF activity may be of interest for further exploration in animal models of Rett syndrome.

MeSH terms

  • Adrenocorticotropic Hormone / analogs & derivatives*
  • Adrenocorticotropic Hormone / therapeutic use
  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Brain-Derived Neurotrophic Factor / metabolism
  • Child
  • Female
  • Humans
  • Methyl-CpG-Binding Protein 2 / genetics
  • Models, Biological*
  • Mutation
  • Neuroprotective Agents / therapeutic use*
  • Peptide Fragments / therapeutic use*
  • Rett Syndrome / drug therapy*
  • Rett Syndrome / genetics


  • Brain-Derived Neurotrophic Factor
  • MECP2 protein, human
  • Methyl-CpG-Binding Protein 2
  • Neuroprotective Agents
  • Peptide Fragments
  • ACTH (4-7), Pro-Gly-Pro-
  • Adrenocorticotropic Hormone